This is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Since not all gene expression changes observed in a tumor are causal to cancer development, the authors demonstrate an approach based on multiple concerted disruption (MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations. IPA (version 8.5) was used. Specifically, the core and comparison analyses were used, with focus on canonical signaling pathways.

The authors demonstrated that “a multi-dimensional genomic approach is superior to analysis of one or two genomic dimensions alone. Each additional genomic dimension surveyed increases the amount of aberrant gene expression that can be explained within individual samples. As a by-product, when examining across a sample set, multi-dimensional genomic analysis can identify relevant genes that may be overlooked due to low frequencies of disruption by the individual mechanisms. The increased frequency of gene disruption detected, due to the consideration of multiple mechanisms of disruption, could potentially reduce the sample size of study cohort needed for gene discovery.”

Figure 5 below and Figure 8 above demonstrate the scientific conclusions that were facilitated by IPA analysis. Click on each image to enlarge it.